The broad objectives of this research plan are to investigate 3 sorts of hormonal or locally-produced agents that affect mineral metabolism in bone. Studies will focus on: 1. Calcitonin; 2. Nonpeptide factors (especially prostaglandins); and 3. Parathyroid hormone. Calcitonin receptors in bone will be characterized, and the control of their modulation and role in "escape" from the biological actions of the peptide will be studied. Calcitonin biosynthesis in normal and malignant thyroid C-cells and in other tissues will be investigated. Additional studies in human medullary thyroid carcinoma will focus on cellular immune mechanisms, pharmacological control, and epidemiology. New studies on two prostaglandin-producing tumors in animals will serve as models for the hypercalcemias of cancer; these include examination of the mechanisms of action of prostaglandins in bone, the role of local prostaglandin production by bone cells, and the metabolism of prostaglandins by bone. Studies of parathyroid hormone will probe its mechanisms of action on bone cells including localization and characterization of its receptors, and the role of vitamin D in parathyroid hormone biosynthesis and release. The experiments proposed are designed to investigate several fundamental aspects of hormones affecting mineral metabolism in in vitro and animal models and to relate these findings to clinically important disorders of bone metabolism in man.